# 270 - References

# References

Schizophrenia and related psychoses
CHAPTER 1
G-­CSF in the face of a low or declining neutrophil count may mask an impending neutropenia or agranulocytosis, leading to dire consequences. The long-­term safety of 
G-­CSF has not been determined but bone density and spleen size should probably be 
monitored.
‘When required’ G-­CSF, to be administered if neutrophils drop below a defined 
threshold, may allow rechallenge with clozapine of patients in whom lithium is insufficient to prevent ‘dipping’ of WCC below the normal range. Again, this strategy risks 
masking a severe neutropenia/agranulocytosis. It is also likely to be practically difficult 
to manage outside a specialist unit, as frequent blood testing (twice to three times a 
week) is required, as well as immediate access to medical review and the G-­CSF itself.
Consultation with a haematologist and discussion with the medical adviser at the 
clozapine monitoring service are essential before considering the use of G-­CSF. A 
patient’s individual clinical circumstances should be considered. In particular, patients 
should be considered to be very high risk for rechallenge with clozapine if the first episode of dyscrasia fulfilled any of the following criteria, all of which suggest that the low 
counts are clozapine-­related:
■
■inconsistent with previous WCCs (i.e. not part of a pattern of repeated low WCCs)
■
■occurred within the first 18 weeks of treatment
■
■severe (neutrophils <0.5×109/L) or
■
■prolonged.
While G-CSF has been reported as allowing successful rechallenge with clozapine in 
some people with previous episodes of clozapine-­induced neutropenia,41 the available 
evidence should exclude this course of action for someone with a true clozapine-­related 
agranulocytosis.42
Lithium is indicated in the management of patients with:
■
■low initial WCC (<4×109/L) or neutrophils (< 2.5×109/L)
■
■leucopenia (WCC <3×109/L) or neutropenia (neutrophils <1.5×109/L) thought to be 
linked to benign ethnic neutropenia. Such patients may be of African or Middle 
Eastern descent, have no history of susceptibility to infection and have morphologically normal white blood cells3
■
■recurrent ‘amber’ results during clozapine treatment
■
■a ‘red’ result probably unrelated to clozapine.
References
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7. Li XH, et al. The prevalence of agranulocytosis and related death in clozapine-­treated patients: a comprehensive meta-­analysis of observational 
studies. Psychol Med 2020; 50:583–594.

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The Maudsley® Prescribing Guidelines in Psychiatry
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